Abstract
THE human immunodeficiency virus type I (HIV-1) nuclear protein Tat is a potent activator of viral gene transcription1,2. Activation by Tat requires a cis-acting element, the transactivation response (TAR) site, located immediately downstream of the transcription start site3–5. Several observations suggest that TAR functions as the nascent RNA product of the HIV long-terminal-repeat promoter (for a review, see ref. 6). Indeed, Tat protein and several cellular proteins bind directly to nascent TAR RNA in vitro7–10. The significance of these in vitro interactions remains to be established. Here we report that Tat can activate transcription when bound to nascent RNA through the RNA-binding domain of another HIV-1 protein, Rev. Rev is a sequence-specific RNA-binding protein, which interacts with the viral RNA element RRE (refs 11-15). A Tat-Rev fusion protein efficiently activates transcription from an HIV-1 promoter derivative, in which TAR has been replaced by the RRE. We conclude that activation of transcription by Tat can occur by direct binding to nascent RNA, and that the sole function of TAR may be to provide a Tat-binding site. Our results further suggest that cellular proteins that bind specifically to TAR RNA or TAR DNA may not be essential for Tat-responsiveness.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Arya, S. K., Guo, C., Josephs, S. J. & Wong-Staal, F. Science 229, 69–73 (1985).
Sodroski, J. G., Rosen, C. A., Goh, W. C. & Haseltine, W. A. Science 228, 1430–1434 (1985).
Rosen, C. A., Sodroski, J. G. & Haseltine, W. A. Cell 41, 813–823 (1985).
Hauber, J. & Cullen, B. R. J. Virol. 62, 673–679 (1988).
Jakobovits, A., Smith, D. H., Jakobovits, E. B. & Capon, D. J. Molec. cell. Biol. 8, 2555–2561 (1988).
Sharp, P. A. & Marciniak, R. A. Cell 59, 229–230 (1989).
Dingwall, C. et al. Proc. natn. Acad. Sci. U.S.A. 86, 6925–6929 (1989).
Gaynor, R., Soultanakis, E., Kuwabara, M., Garcia, J. & Sigman, D. S. Proc. natn. Acad. Sci. U.S.A. 86, 4858–4862 (1989).
Gatignol, A., Kumar, A., Rabson, A. & Jeang, K.-T. Proc. natn. Acad. Sci. U.S.A. 86, 7828–7832 (1989).
Marciniak, R. A., Garcia-Blanco, M. A. & Sharp, P. A. Proc. natn. Acad. Sci. U.S.A. 87, 3624–3628 (1990).
Zapp, M. L. & Green, M. R. Nature 342, 714–716 (1989).
Daly, T. J., Cook, K. S., Gary, G. S., Maione, T. E. & Rusche, J. R. Nature 342, 816–819 (1989).
Cochrane, A. W., Chen, C.-H. & Rosen, C. A. Proc. natn. Acad. Sci. U.S.A. 87, 1198–1202 (1990).
Malim, M. H. et al. Cell 60, 675–683 (1990).
Heaphy, S. et al. Cell 60, 785–693 (1990).
Ptashne, M. Nature 335, 683–689 (1988).
Green, M. R. & Zapp, M. L. Nature 338, 200–201 (1989).
Kao, S.-Y., Calman, A. F., Luciw, P. A. & Peterlin, B. M. Nature 330, 489–493 (1987).
Selby, M. J., Bain, E. S., Luciw, P. A. & Peterlin, B. M. Genes Dev. 3, 547–558 (1989).
Garcia, J. A., Harrich, D., Pearson, L. Mitsuyasu, R. & Gaynor, R. B. EMBO J. 7, 3143–3147 (1988).
Sadaie, M. R. et al. Proc. natn. Acad. Sci. U.S.A. 85, 9224–9228 (1988).
Green, M. & Lowenstein, P. M. Cell 55, 1179–1188 (1988).
Ruben, S. et al. J. Virol. 63, 1–8 (1989).
Kuppuswamy, M., Subramanian, T., Srinivasan, A. & Chinnadurai, G. Nucleic Acids Res. 17, 3551–3561 (1989).
Rappaport, J., Lee, S.-J., Khalili, K. & Wong-Staal, F. New Biologist 1, 101–110 (1989).
Frankel, A. D., Biancalana, S. & Hudson, D. Proc. natn. Acad. Sci. U.S.A. 86, 7397–7401 (1989).
Hauber, J., Malim, M. & Cullen, B. R. J. Virol. 63, 1181–1187 (1989).
Cullen, B. R. Cell 46, 973–982 (1986).
Malim, M. H., Hauber, J., Fenrick, R. & Cullen, B. R. Nature 335, 181–183 (1988).
Charnay, P. et al. Cell 38, 251–263 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Southgate, C., Zapp, M. & Green, M. Activation of transcription by HIV-1 Tat protein tethered to nascent RNA through another protein. Nature 345, 640–642 (1990). https://doi.org/10.1038/345640a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/345640a0
This article is cited by
-
Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA
Nature Communications (2018)
-
RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation
Nature Structural & Molecular Biology (2010)
-
Transcriptional regulation by small RNAs at sequences downstream from 3′ gene termini
Nature Chemical Biology (2010)
-
A simple and rapid TAR-dependent in vitro transcription assay using T cell nuclear extracts and synthetictat1-86 protein
Journal of Biomedical Science (1995)
-
Transcriptional antitermination
Nature (1993)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.